将药物精确输送到肿瘤部位和肿瘤的耐热性仍然是光热疗法（PTT）的主要挑战。生长抑素受体 2 (SSTR2) 被认为是 SCLC 精准治疗的理想靶点。我们开发了一种靶向纳米药物递送系统，包含共封装 Cypate 和藤黄酸 (GA) 的抗 SSTR2 单克隆抗体 (MAb) 表面修饰纳米颗粒。形成的SGCPNs表现出优异的单分散性、生理稳定性、良好的生物相容性和高效的光热转换效率。 SGCPNs很快被SSTR2过表达的SCLC细胞内化，在酸性和近红外（NIR）激光照射环境下触发GA释放，导致它们从溶酶体逃逸到细胞质，然后扩散到细胞核中。 SGCPNs不仅可以降低细胞存活率，还可以抑制热休克蛋白90（HSP90）的活性。 SGCPNs 可以在体内精确递送至 SSTR2 阳性 SCLC 的异种移植肿瘤。近红外激光照射后，SGCPNs 治疗显示出显着的肿瘤消退。总之，SGCPNs 为靶向 SCLC 提供了一种新的化学光热协同治疗策略。© 2024 UICC。

The precise delivery of drugs to tumor sites and the thermoresistance of tumors remain major challenges in photothermal therapy (PTT). Somatostatin receptor 2 (SSTR2) is proposed as an ideal target for the precise treatment of SCLC. We developed a targeting nano-drug delivery system comprising anti-SSTR2 monoclonal antibody (MAb) surface-modified nanoparticles co-encapsulating Cypate and gambogic acid (GA). The formed SGCPNs demonstrated excellent monodispersity, physiological stability, preferable biocompatibility, and resultant efficient photothermal conversion efficacy. SGCPNs were quickly internalized by SSTR2-overexpressing SCLC cells, triggering the release of GA under acidic and near-infrared (NIR) laser irradiation environments, leading to their escape from lysosomes to the cytosol and then diffusion into the nucleus. SGCPNs can not only decrease the cell survival rate but also inhibit the activity of heat shock protein 90 (HSP90). SGCPNs can be precisely delivered to xenograft tumors of SSTR2-positive SCLC in vivo. Upon NIR laser irradiation, therapy of SGCPNs showed significant tumor regression. In conclusion, SGCPNs provide a new chemo-photothermal synergistic treatment strategy for targeting SCLC.© 2024 UICC.